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Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 145 records · Page 8Linked to original sources
PubMed1993

Group II self-splicing introns in bacteria.

Like nuclear premessenger introns, group II self-splicing introns are excised from primary transcripts as branched molecules, containing a 2'-5' phosphodiester bond. For this reason, it is widely believed that the ribozyme (catalytic RNA) core of group II introns, or some evolutionarily related molecule, gave rise to the RNA components of the spliceosomal splicing machinery of the eukaryotic nucleus. One difficulty with this hypothesis has been the restricted distribution of group II introns. Unlike group I self-splicing introns, which interrupt not only organelle primary transcripts, but also some bacterial and nuclear genes, group II introns seemed to be confined to mitochondrial and chloroplast genomes (reviewed in ref. 6). We now report the discovery of group II introns both in cyanobacteria (the ancestors of chloroplasts) and the gamma subdivision of purple bacteria, or proteobacteria, whose alpha subdivision probably gave rise to mitochondria. At least one of these introns actually self-splices in vitro.

Amino Acid Sequence↗
PubMed1993

Defective calcium response in B-chronic lymphocytic leukemia cells. Alteration of early protein tyrosine phosphorylation and of the mechanism responsible for cell calcium influx.

To study defective signal transduction via the Ag receptor of B-chronic lymphocytic leukemia cells (B-CLL), we examine in this report the Ca2+ response triggered by anti-mu antibody in 23 patients previously classified in three phenotypic groups. Altered Ca2+ changes are essentially found in CLL group II whose leukemic cells are characterized by a marked expression of the CD11b Ag. B-CLL cells from patients with a defective Ca2+ response present an altered pattern of protein tyrosine phosphorylation after anti-mu stimulation in comparison with normal human B cells and B-CLL cells from patients having a normal Ca2+ response. Most of the proteins usually tyrosine phosphorylated after the triggering of cell-surface IgM are concerned. This includes the gamma 1 isoform of phospholipase C, although the protein is normally present in B-CLL cells. These findings suggest that the interruption of the phosphoinositide pathway in B-CLL cells is very proximal, at the level in the signaling cascade between activated surface Ig receptors and protein tyrosine kinases. Simultaneously, we demonstrate that some low responding patients exhibit a decreased Ca2+ response to thapsigargin, an agent known to release intracellular Ca2+ without inositol 1,4,5-trisphosphate production. This suggests that an altered functioning of the mechanism leading to the cell Ca2+ influx in B cells can be also involved in the decreased Ca2+ response observed in B-CLL cells.

Animals↗
PubMed1993

Group I introns in the liverwort mitochondrial genome: the gene coding for subunit 1 of cytochrome oxidase shares five intron positions with its fungal counterparts.

The complete nucleotide sequence of the mitochondrial DNA (mtDNA) from a liverwort, Marchantia polymorpha, contains thirty-two introns. Twenty-five of these introns possess the characteristic secondary structures and consensus sequences of group II introns. The remaining seven are group I introns, six of which happen to interrupt the gene coding for subunit 1 of cytochrome oxidase (cox1). Interestingly, the insertion sites of one group II and four group I introns in the cox1 gene coincide with those of the respective fungal mitochondrial interns. Moreover, comparison of the four group I introns with their fungal counterparts shows that group I introns inserted at identical genomic sites in different organisms are indeed related to one another, in terms of the peptide sequences generated from the complete or fragmental ORFs encoded by these introns. At the same time, the liverwort introns turned out to be more divergent from their fungal cognates than the latter are from one another. We therefore conclude that vertical transmission from a common ancestor organism is the simplest explanation for the presence of cognate introns in liverwort and fungal mitochondrial genomes.

Amino Acid Sequence↗
PubMed1993

Sequence of the mitochondrial gene encoding subunit I of cytochrome oxidase in Saccharomyces douglasii.

We have determined the complete sequence of the mitochondrial (mt) gene (COXI) coding for cytochrome oxidase subunit I of Saccharomyces douglasii. This gene is 7238 bp long and includes four introns. The salient feature of the S. douglasii COXI gene is the presence of two introns, Sd.ai1 and Sd.ai2, which have not been observed in S. cerevisiae genes. Both are group-I introns and are located at novel positions compared with the S. cerevisiae COXI. Interestingly, one of these introns (the second one) is inserted at the same position as intron 2 of COXI of Kluyveromyces lactis and also as intron 8 of the same gene in Podospora anserina. The ORFs contained in these three introns display a high degree of similarity. Comparisons of exonic and intronic sequences of the COXI of two Saccharomyces species reinforces our previous conclusions: the evolution of mt genes in yeast obeys different rules to those found in vertebrates.

Amino Acid Sequence↗
PubMed1993

The nad6 gene and the exon d of nad1 are co-transcribed in wheat mitochondria.

The exon d of nad1 is located 993 bp upstream of the nad6 gene in the wheat mitochondrial genome. Transcription analyses of both sequences (nad1 exon d and the nad6 gene) were done by Northern hybridization using RNA from wheat seedlings and tissue cultures derived from immature embryos. A complicated pattern was generated with a probe including exon d of nad1 and the whole nad6 gene. An 0.71-kb transcript is specific to nad1 exon d whereas a 1.2-kb transcript is specific to the nad6 gene. Three larger transcripts hybridize to both probes suggesting that nad1 exon d and nad6 are co-transcribed. This co-transcription has been directly demonstrated by cDNA synthesis on mtRNAs and sequencing of the PCR amplification product.

Base Sequence↗
PubMed1993

[Influence of the position of the arm on the level of clinical arterial pressure].

The position of the arm in relation to the heart is one of the factors responsible for variations in arterial blood pressure. The purpose of this study was to confirm these variations and their diagnostic and therapeutic consequences. The blood pressure of 59 subjects was measured in supine position with or without support, this support being a device, recently developed by Swedish physicians, that brings the radial notch of the ulna at heart level. The results obtained confirmed the existence of variations in blood pressure values according to the position of the arm in relation to the heart. When measured with the support, blood pressure fell by 5 mmHg for systolic pressure and 4.6 mmHg for diastolic pressure. These results prove the need for standardization of blood pressure measurement in supine position. It is permissible to believe that at this moment a non-negligible proportion of patients (12 percent in our series) is either wrongly regarded as hypertensive or overtreated. In addition, the blood pressure variations induced by the brachial support should be taken into account in the analysis of future epidemiological studies. We conclude that using the brachial support can be recommended for a better evaluation of supine blood pressure measurements.

Arm↗
PubMed1993

Early and semi-early surgery for scoliosis caused by hemivertebrae--indications and results.

We report a series of 50 congenital scolioses due to hemivertebrae. This malformation was responsible for progressive deformity, largely predominant on the frontal plane. The average follow-up was 5 years and 3 months. Seven patients had mature bones. The series comprised 31 girls and 19 boys. Three types of operations were performed: (a) hemivertebrae resection (5 cases); (b) early, most posterior convexity fusion carried out before the age of 6 years (26 cases), and (c) semi-early convexity fusion performed between the ages of 6 and 12 years (19 cases). The results obtained in children with a more than 2 years' follow-up were: (a) early convexity fusion (18 cases): 7 epiphyseodesis effects, 6 graft effects and 4 failures; (b) semi-early convexity fusion (16 cases): 6 epiphyseodesis effects, 8 graft effects and 2 failures; (c) hemivertebrae resection (5 cases): moderate gain that remained stable in 4/5 cases.

Adolescent↗
PubMed1993

Hand performance of French children on a finger-tapping test in relation to handedness, sex, and age.

Hand performance and laterality scores on a unimanual tapping test were studied in relation to age, sex, and handedness in a sample of 209 French children. Each child performed three trials with each hand. Older children were faster, but differences between hands were not related to age. Right-handed girls were more lateralized than right-handed boys. Left- and right-handers could be differentiated more clearly by tapping speed than by variability of tapping. A subsample of 36 right-handers were retested to estimate reliability. The coefficients were high, especially when using the mean of trials as the dependent variable. Correlations between performance on the tapping task and another test of hand-efficiency (dot-filling task) were low.

Child↗
PubMed1992

Amino acid sequence of band-3 protein from rainbow trout erythrocytes derived from cDNA.

In this report we present the first complete band-3 cDNA sequence of a poikilothermic lower vertebrate. The primary structure of the anion-exchange protein band 3 (AE1) from rainbow trout erythrocytes was determined by nucleotide sequencing of cDNA clones. The overlapping clones have a total length of 3827 bp with a 5'-terminal untranslated region of 150 bp, a 2754 bp open reading frame and a 3'-untranslated region of 924 bp. Band-3 protein from trout erythrocytes consists of 918 amino acid residues with a calculated molecular mass of 101 827 Da. Comparison of its amino acid sequence revealed a 60-65% identity within the transmembrane spanning sequence of band-3 proteins published so far. An additional insertion of 24 amino acid residues within the membrane-associated domain of trout band-3 protein was identified, which until now was thought to be a general feature only of mammalian band-3-related proteins.

Amino Acid Sequence↗
PubMed1992

Erythrocytosis in renal allograft recipients. Benefit of staggered venous erythropoietin measurements.

Two adult renal allograft recipients experienced erythrocytosis--one in acute form--within 3 months of grafting. Involvement of well functioning transplanted kidneys was unlikely whereas staggered erythropoietin measurements detected a high gradient in front of venous remnant kidneys. Because of these results bilateral nephrectomy was performed, which cured polycythaemia. Multiple events leading to polycythaemia after renal transplantation are reviewed and diagnosis and therapeutic schedules are proposed.

Adult↗
PubMed1992

HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in nef p27 and gag p25 proteins.

Cellular immunogenicity of env gp160, nef p27, and gag p55 proteins of human immunodeficiency virus type 1 (HIV-1) was studied in mice immunized with vaccinia virus recombinants. Proliferative responses of spleen cells were comparable against env gp160, nef p27, and gag p25 recombinant proteins. No specific activity was observed against gag p18 protein. Env, nef, and gag-specific T-cell lines were generated by repeated stimulation of immune spleen cells with recombinant HIV-1 proteins. They were CD4 positive, proliferative, and also cytotoxic against HIV-transfected target cells. Specificity of the T-cell response against nef and gag protein was analyzed with synthetic peptides. Peptides nef 15, nef 16, and gag AM-30 were, respectively, reactive in nef- and gag-specific proliferative and cytolytic assays. The three peptides described have a relatively conserved amino acid sequence among HIV isolates and appear broadly immunoreactive among species.

Amino Acid Sequence↗
PubMed1992

Activation of the catalytic core of a group I intron by a remote 3' splice junction.

Over 1000 nucleotides may separate the ribozyme core of some group I introns from their 3' splice junctions. Using the sunY intron of bacteriophage T4 as a model system, we have investigated the mechanisms by which proximal splicing events are suppressed in vitro, as well as in vivo. Exon ligation as well as cleavage at the 5' splice site are shown to require long-range pairing between one of the peripheral components of the ribozyme core and some of the nucleotides preceding the authentic 3' splice junction. Consistent with our three-dimensional modeling of the entire sunY ribozyme, we propose that this novel interaction is necessary to drive 5' exon-core transcripts into an active conformation. A requirement for additional stabilizing interactions, either RNA-based or mediated by proteins, appears to be a general feature of group I self-splicing. A role for these interactions in mediating putative alternative splicing events is discussed.

Base Sequence↗
PubMed1992

Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment.

Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6-12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV-specific CTL response.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Burkitt's lymphoma: an exceptional cause of testicular tumor].

Based on a case of Burkitt's lymphoma presenting in the form of a testicular mass in a 66 year old man, the authors stress the importance of making the diagnosis as early as possible. This malignant lesion has one of the greatest capacities for proliferation and any delay in treatment can decrease the chances of curability of the tumour.

Aged↗
PubMed1992

[Neurological complications of surgery for spinal deformities].

The aim of this study was to precisely analyse the physio-pathogenic mechanisms, bring to light the risk factors, and find a more practical way of proceeding in spinal surgery. Out of 667 spinal instrumentation surgical operations carried out between 1980-1989, we found 33 (4.8 per cent) neurological complications and have divided them into 2 groups: 7 peripheral complications, 26 cord and central complications. After further analysis, especially of the cord complications (2.5 per cent), we were able to pick out the factors which influence the rate of neurological complications and their evolution: secondary aetiology and the kyphotic composition of spinal deformation, and above all the notion of cord at risk. The delay of cord complications and especially the relation between the severity of the neurological syndrome and its evolution is extremely important. Somesthesic evoked potential monitoring confirmed that per operative diagnosis of a cord injury is possible. The steps to take when confronted with neurological complications, depend on the results of many examinations: pre and post-operative neurological evaluations electrophysiological exploration of the cord and neuro radiological explorations (myelography, scanner and IRM). This helps to complete aetiology and eliminate mechanical causes, which are the only positive indications of iterative surgery. The problems of instrumentation removal in emergency and the legal-medical aspect brought on by this type of complication are discussed.

Humans↗
PubMed1991

Function of P11, a tertiary base pairing in self-splicing introns of subgroup IA.

There is phylogenetic evidence for the existence of a new pairing in subgroup IA1 self-splicing introns. This tertiary interaction, called P11, which is extraneous to the catalytic centre of these ribozymes was modelled after a "pseudoknot" and grafted by computer modelling on the common core structure of group I introns that was recently proposed by Michel & Westhof. In order to probe the function of the P11 pairing, we mutated the P11 helix in the intron of the large ribosomal precursor of Saccharomyces cerevisiae mitochondria (Sc.LSU). Our experimental data show that the P11 pairing plays a role in stabilizing the overall fold of the RNA molecule. While P11 is not essential for self-splicing activity in vitro, mutants with disrupted P11 require higher concentration of MgCl2 for self-splicing. By contrast, mutants with a reinforced P11 pairing (via introduction of several G.C base-pairs) self-splice more efficiently than the wild-type at 55 degrees C. Based on this work, the possible engineering of new stable versions of the ribozyme is discussed.

Base Composition↗